FUNGAL SINUSITIS

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FUNGAL SINUSITIS

• David Gleinser, MD
• Patricia Maeso, MD
• The University of Texas Medical Branch (utmb
  health)
• Department of OtolaryngologyGrand Rounds
  PresentationJanuary 30, 2012

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Introduction

• Fungi are ubiquitous
• Immune system keeps organisms suppressed
• Most infections are benign, non-invasive
• Immunocompromised higher risk of invasive
  disease
• Non-invasive vs. invasive

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Basic Mycology

• 20,000 1.5 million fungal species
• Few dozen species cause human infection
• Forms yeast or mold
• Yeast
• Unicellular
• Reproduce asexually by budding
• Pseudohyphae when bud doesnt detach from yeast
• Mold
• Multicellular
• Grow by branching hyphae

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Pseudohyphae vs. Hyphae
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Basic Mycology

• Spore
• Reproductive structure produced in unfavorable
  conditions
• Withstand many adverse conditions
• Favorable environment ? growth
• Inhalation of spores most common way fungi
  infiltrate sinuses to cause disease

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Basic Mycology

• Microscopic Appearance of Specific Fungi
• Aspergillus
• Septated hyphae with branching at 45
• Mucromycosis
• Nonseptated hyphae with branching at 90

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Aspergillus
Note septations (yellow arrows) and 45 degree
branching (red arrows)
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Note the 90 degree branching and lack of
septations
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Classification of Infection

• Non-invasive
• Saprophytic fungal infestation
• Sinus fungal ball (mycetoma)
• Allergic fungal sinusitis
• Invasive
• Acute fulminant invasive fungal sinusitis
• Chronic invasive fungal sinusitis
• Granulomatous invasive fungal sinusitis

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Saprophytic Fungal Infestation

• Visible growth of fungus on mucus crusts without
  invasion
• Minimal to no sinonasal symptoms
• Diagnosis
• Endoscopic visualization of crusts with fungi
• Treatment
• Removal of crusts
• Nasal saline irrigations
• Weekly nasal endoscopy with removal of crusts
  until disease process resolves

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Sinus Fungal Ball (Mycetoma)

• Sequestration of fungal elements within a sinus
  without invasion or granulomatous changes
• Inhaled spores ? grow while evading host immune
  system (no invasion)
• Aspergillus most common species
• Maxillary sinus most often involved (70-80 of
  cases)

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Sinus Fungal Ball (Mycetoma)

• Clinically
• Symptoms due to mass effect and sinus obstruction
• Presents similar to rhinosinusitis
• Congestion, facial pain, headache, rhinorrhea
• Physical examination
• Mild to minimal mucosal inflammation
• Polyps in 10 of cases

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Sinus Fungal Ball (Mycetoma)

• Diagnosis
• CT Scan
• Single sinus in 59-94 of cases (maxillary)
• Complete or subtotal opacification of sinus
• Radiodensities within the opacifications
• Due to increased heavy metal content
• Bony sclerosis destruction is rare (3.6-17 of
  cases)
• Biopsy fungal elements

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Fungal Ball
Images show thickening of bony walls (short
arrows) and heterodense material within the sinus
with calcifications (long arrows)
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Sinus Fungal Ball (Mycetoma)

• Treatment
• Complete surgical removal of fungal ball
• Irrigation of involved sinuses
• Antifungal therapy
• Only if patient is high risk for invasive disease
  (very rare)
• Severely immunocompromised
• Continued recurrence of disease despite proper
  medical/surgical management
• Consider topical antifungal irrigation first and
  then systemic therapy if no improvement

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Fungal Ball
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Allergic Fungal Sinusitis

• Fungal colonization resulting in allergic
  inflammation without invasion
• IgE mediated response to fungal protein
• Symptoms
• Nasal obstruction (gradual)
• Rhinorrhea
• Facial pressure/pain
• Sneezing, watery/itchy eyes
• Periorbital edema

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Allergic Fungal Sinusitis

• Diagnostic Criteria
• Eosinophlic mucin
• Nasal polyposis
• Radiographic findings
• Immunocompetance
• Allergy to fungi

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Allergic Fungal Sinusitis

• Eosinophilic Mucin
• Pathognemonic
• Thick, tenacious and highly viscous
• Tan to brown or dark green in appearance
• Microscopic examination
• Branching fungal hyphae
• Sheets of eosinophils
• Charcot-Leyden crystals
• Breakdown of cells by enzymes produced by
  eosinophils
• Slender and pointed at each end
• Pair of hexagonal pyramids joined at bases

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Eosinophilic Mucin
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Allergic Fungal Sinusitis

• Radiographic findings
• CT
• Unilateral (78 of cases)
• Sinus expansion
• Bone destruction in 20 of cases
• More often in advanced or bilateral disease
• Double Densities
• Heterogeneity of signal ? increased heavy metal
  content (iron and manganese) and calcium salts

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Allergic Fungal Sinusitis
Arrows show double densities. Note sinus expansion
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Allergic Fungal Sinusitis
Double densities (arrows). Expansion of sinus
with extension of disease into the nasal cavity
(star)
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Allergic Fungal Sinusitis

• Radiographic findings
• MRI
• Variable signal intensity on T1 (usually
  hyperintense)
• T2 hypointense central portion (low water
  content of mucin) with peripheral enhancement due
  to edema

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Allergic Fungal Sinusitis
T1 MRI high signal intensity of debris
T2 MRI central area of low intensity surrounded
by high intense signal
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Allergic Fungal Sinusitis
T1 MRI high signal intensity of debris
T2 MRI central area of low intensity surrounded
by high intense signal
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Allergic Fungal Sinusitis

• Allergy to Fungi
• Most patient with AFS will have allergy to fungus
  causing disease
• Manning et al
• Prospective study
• Compared
• 8 patients with AFS and ()culture with Bipolaris
• 10 controls with chronic rhinosinusitis
• All 8 patients showed () skin testing, RAST, and
  ELISA to Bipolaris
• 8 of 10 controls (-) for all tests
• IgE levels gt 1000 IU/mL

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Allergic Fungal Sinusitis

• Treatment
• Surgical
• Remove all mucin
• Provide permanent drainage and ventilation of
  affected sinuses
• Systemic /- topical steroids
• Systemic steroids decrease rate of recurrence
• Course can range from 2-12 months
• Schubert showed that longer courses had better
  results, but more side effects
• 0.5mg/kg Prednisone starting dose and taper over
  2-3 months

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Allergic Fungal Sinusitis

• Immunotherapy
• Decrease recurrence
• Alleviate need for steroids
• Prospective review
• All patients had surgery and systemic steroids
• One group got immunotherapy, the other did not
• Consisted of fungal and non-fungal antigens to
  which patients were sensitive
• After 1 year
• No requirement for systemic or topical steroids
  by patients in immunotherapy group
• Recurrence of disease significantly less in
  immunotherapy group

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Allergic Fungal Sinusitis

• Immunotherapy
• Folker et al
• Retrospective study
• Compared 11 patients who received immunotherapy
  post-operatively vs. 11 who did not
• Recurrence rates did NOT decrease
• However
• Quality of life scores and mucosal edema were
  much better in those who received immunotherapy

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Acute Fulminant Invasive Fungal Sinusitis

• Patient population
• Most often compromised immune system
• DM, AIDS, hematologic malignancies, organ
  transplant, iatrogenic (chemotherapy and
  steroids)
• Most common fungi
• Aspergillus
• Mucormycosis
• Mucor, Rhizopus, Absidia
• Less common fungi
• Candida
• Bipolaris
• Fusarium

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Acute Fulminant Invasive Fungal Sinusitis

• Pathogenesis
• Spores inhaled ? fungus grows in warm, humid
  sinonasal cavity
• Fungi invade neural and vascular structures with
  thrombosis of feeding vessels
• Necrosis and loss of sensation ? acidic
  environment ? further fungal growth
• Extrasinus extension occurs via bony destruction,
  perineural and perivascular invasion
• Nasal and palate mucosa destroyed
• Facial anesthesia
• Proptosis
• Cranial nerve deficits
• Mental status changes

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Acute Fulminant Invasive Fungal Sinusitis

• Other signs/symptoms
• Fever (most common 90 of cases)
• Loss of sensation over face or oral cavity
• Ulceration of face and sinonasal/palatal mucosa
• Rhinorrhea, facial pain/anesthesia, headaches
• Seizures, CN deficits
• Fast progressing symptoms
• In some cases, hours to days till death!

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Acute Fulminant Invasive Fungal Sinusitis

• Endoscopic findings
• Loss of sensation and change in appearance of
  mucosa (pale or black)
• Most consistent finding
• Ulcerations and black mucosa are late findings
• Serial examinations are required

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Acute Fulminant Invasive Fungal Sinusitis

• Biopsy Culture
• Should always be performed when
• Suspect fungal disease
• Change in sensation or color of mucosa
• Any immunocompromised patient with signs of
  sinusitis who fails to improve after 72 hours of
  IV antibiotics
• Where?
• Diseased mucosa (pale, insensate, ulcerative,
  black)
• Normal appearance/sensation
• Middle turbinate most common spot for AFIFS
  (67)
• Septum 24 of cases
• Must request silver staining
• Culture
• Very difficult to get () result, especially with
  Mucormycosis

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Acute Fulminant Invasive Fungal Sinusitis

• Radiographic studies
• CT sinus
• MRI to assess tissue invasion, and orbital,
  intracranial, or neural involvement
• Findings
• CT
• Bone erosion and extrasinus extension classic
  finding
• Severe, unilateral mucosal thickening
• Thickening of periantral fat planes

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CT scans Left image Destruction of medial wall
of orbit with extension of disease into the
orbit. Right image Destruction of medial and
inferior walls of the orbit with extension of
disease into the orbit
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Axial CT scans. Left image invasion through
lateral wall of the sphenoid sinus and into the
cavernous sinus. Right image lack of
enhancement of the cavernous sinus due to fungal
thrombosis
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Acute Fulminant Invasive Fungal Sinusitis

• MRI
• Obliteration of the periantral fat
• Leptomeningeal enhancement (intracranial
  extension)
• Granuloma formation
• Hypointense on T1 and T2
• Extrasinus extension
• Cavernous sinus involvement
• Absent flow void of carotid
• Soft tissue thickening of the involved sinus

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Axial MRI, T2 left sphenoid sinus with central
hypointense region with surrounding
hyperintensity. Flow void in left cavernous
sinus absent (arrow)
Axial MRI, T2 Acute infarction of the left
temporal lobe in same patient
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Acute Fulminant Invasive Fungal Sinusitis

• Combination of medical and surgical treatment
• Medical
• Correct the underlying compromised state
• Reverse DKA and improve hydration
• 80 survival if done promptly
• Absolute neutrophil count
• lt 1000 poor prognosis
• WBC transfusion and granulocyte colony
  stimulating factor to increase ANC

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Acute Fulminant Invasive Fungal Sinusitis

• Medical treatment
• Systemic antifungals
• Amphotericin B infusion
• 1mg/kg/day
• Serious side effects
• ototoxicity, nephrotoxicity (occurs in 80 of
  cases)
• Lipid-based form of Amphotericin B
• More expensive
• Less toxic
• Can achieve higher concentrations of drug
• Voriconazole or itraconazole
• Used most often when Aspergillus involved
• Much less toxic than Amphotericin B
• Mucormycosis are resistant to these

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Acute Fulminant Invasive Fungal Sinusitis

• Topical Amphotericin B rinses
• Have shown some success, but mixed results
• Surgical treatment
• Goals
• Decrease pathogen load
• Remove devitalized tissue
• Establish pathways for sinus drainage
• Debride until clear, bleeding margins

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Acute Fulminant Invasive Fungal Sinusitis

• Endoscopic vs. Open procedures
• Recommend endoscopic in early course of disease
• Decreased morbidity
• Similar survival rates as open procedures
• Advanced disease (orbit, palatal, skin)
• Open approach required
• Once disease has gone intracranial, prognosis is
  very poor
• Must be considered prior to partaking in
  extensive surgical resection

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Acute Fulminant Invasive Fungal Sinusitis

• Retrospective review out of Turkey
• Examined treatment of AFIFS
• 26 patient
• 19 endoscopic resection
• 7 open resection
• 5 orbital exenteration (2 survived)
• All patients with skull base/intracranial
  extension died
• Overall mortality rate 50
• Survival rates
• Endoscopic 90 (less severe disease)
• Open 57
• In those who died, Mucormycosis were involved in
  62 of cases
• More aggressive with early orbital and
  intracranial invasion

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Acute Fulminant Invasive Fungal Sinusitis

• Prognosis
• Mortality rate 18-80
• Early detection and treatment much better
  chance of survival
• Intracranial involvement
• Most predictive indicator for mortality
• 70 mortality rate
• Absolute Neutrophil Count (ANC) lt 1000
• Worse prognosis
• Recovery from neutropenia most predictive
  indicator for survival
• Mucormycosis more fatal
• Diabetics tend to do worse
• Greater incidence of Mucormycosis in these
  patients

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Chronic Invasive Fungal Sinusitis

• Slower disease process than acute
• Rare
• Biggest difference
• Most patients are immunocompetent
• Common fungi
• Aspergillus (most common - gt80 of cases)
• Bipolaris
• Candida
• Mucormycosis

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Chronic Invasive Fungal Sinusitis

• Signs/Symptoms
• Similar to symptoms of chronic rhinosinusitis
• Nasal congestion, rhinorrhea, facial pressure,
  headaches, polyposis
• Proptosis, visual changes, anesthesia of skin,
  epistaxis
• More concerning
• Does not respond to antibiotics
• Worsens with steroids

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Chronic Invasive Fungal Sinusitis

• Diagnosis
• Full HN examination with nasal endoscopy
• Nasal polyps, thick mucus
• Rarely find ulcerations
• Biopsy if suspect fungal disease or note any
  changes
• CT MRI
• Similar findings to AFIFS bony destruction,
  extrasinus extension, unilateral

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CT showing destruction of right lateral maxillary
sinus and zygomatic arch
CT showing opacification of left maxillary sinus
with extrasinus extension of disease into the
periantral tissues (arrows)
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Chronic Invasive Fungal Sinusitis

• Diagnosis
• Pathology
• Invasion of blood vessels, neural structures, and
  surrounding mucosa
• Few if any inflammatory cells
• Major difference between acute and chronic
  invasive disease
• No Granuloma formation
• Main difference between chronic invasive fungal
  disease and granulomatous invasive fungal disease

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Chronic Invasive Fungal Sinusitis

• Treatment
• Similar to AFIFS surgical medical
• Surgery
• resect all involved tissue to expose bleeding
  margins
• Systemic antifungals
• Start with Amphotericin B until can rule out
  Mucormycosis
• Best length of treatment not well studied
• Most recommend 3-6 months of therapy
• Topical Amphotericin B sinus rinses
• Close F/U and debridement required
• Biopsy anything that is suspicious as
  asymptomatic recurrence is not uncommon

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Granulomatous Invasive Fungal Sinusitis

• Appears exactly like CIFS
• Very rare
• Presence of multinucleated giant cell granulomas
• Most important difference between Chronic and
  Granulomatous disease
• Aspergillus flavus
• Most often seen in North Africa and Southeast Asia

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Granulomatous Invasive Fungal Sinusitis

• Presentation and work-up are exactly the same as
  CIFS
• Treatment
• Surgical resection to bleeding margins
• Topical antifungal rinses
• Systemic antifungals
• Oral voriconazole or itraconazole
• Minority of authors believe systemic antifungals
  not required
• Close F/U and debridement required
• Biopsy anything that is suspicious as
  asymptomatic recurrence is not uncommon

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Conclusion

• Fungi are ubiquitous
• Disease in immunocompetent is nearly always
  benign, but must consider invasive disease
• Invasive fungal disease must be considered in all
  immunocompromised patients
• Low threshold for biopsy

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Conclusion

• Surgical debridement
• Mainstay of treatment of fungal sinus disease
• Invasive disease debride until clear, bleeding
  margins
• Weigh extent of surgery with prognosis
• Skull base/intracranial involvement very poor
  prognosis even with aggressive therapy
• Systemic antifungals required for invasive
  disease
• Monitor for severe side effects
• Close follow-up with debridement and biopsy of
  any suspicious lesions

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